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Open AccessArticle

LCAT, ApoD, and ApoA1 Expression and Review of Cholesterol Deposition in the Cornea

1
Experimental Atherosclerosis Section, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
2
Advanced Cell Diagnostics, Newark, CA 94560, USA
3
Cornea and Cataract Section, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA
4
Cardiovascular Nutrition Laboratory, Human Nutrition Research Center on Aging at Tufts University nd Tufts University School of Medicine, Boston, MA 02111, USA
5
Boston Heart Diagnostics, Framingham, MA 01702, USA
*
Author to whom correspondence should be addressed.
Deceased.
Biomolecules 2019, 9(12), 785; https://doi.org/10.3390/biom9120785
Received: 25 October 2019 / Revised: 14 November 2019 / Accepted: 15 November 2019 / Published: 26 November 2019
Lecithin:cholesterol acyltransferase (LCAT) is an enzyme secreted by the liver and circulates with high-density lipoprotein (HDL) in the blood. The enzyme esterifies plasma cholesterol and increases the capacity of HDL to carry and potentially remove cholesterol from tissues. Cholesterol accumulates within the extracellular connective tissue matrix of the cornea stroma in individuals with genetic deficiency of LCAT. LCAT can be activated by apolipoproteins (Apo) including ApoD and ApoA1. ApoA1 also mediates cellular synthesis of HDL. This study examined the expression of LCAT by epithelial cells, keratocytes, and endothelial cells, the cell types that comprise from anterior to posterior the three layers of the cornea. LCAT and ApoD were immunolocalized to all three cell types within the cornea, while ApoA1 was immunolocalized to keratocytes and endothelium but not epithelium. In situ hybridization was used to detect LCAT, ApoD, and ApoA1 mRNA to learn what cell types within the cornea synthesize these proteins. No corneal cells showed mRNA for ApoA1. Keratocytes and endothelium both showed ApoD mRNA, but epithelium did not. Epithelium and endothelium both showed LCAT mRNA, but despite the presence of LCAT protein in keratocytes, keratocytes did not show LCAT mRNA. RNA sequencing analysis of serum-cultured dedifferentiated keratocytes (commonly referred to as corneal stromal fibroblasts) revealed the presence of both LCAT and ApoD (but not ApoA1) mRNA, which was accompanied by their respective proteins detected by immunolabeling of the cultured keratocytes and Western blot analysis of keratocyte lysates. The results indicate that keratocytes in vivo show both ApoA1 and LCAT proteins, but do not synthesize these proteins. Rather, keratocytes in vivo must take up ApoA1 and LCAT from the corneal interstitial tissue fluid.
Keywords: cornea; keratocytes; LCAT; ApoA1; ApoD; cholesterol; HDL; atherosclerosis; corneal stromal fibroblasts cornea; keratocytes; LCAT; ApoA1; ApoD; cholesterol; HDL; atherosclerosis; corneal stromal fibroblasts
MDPI and ACS Style

Flores, R.; Jin, X.; Chang, J.; Zhang, C.; Cogan, D.G.; Schaefer, E.J.; Kruth, H.S. LCAT, ApoD, and ApoA1 Expression and Review of Cholesterol Deposition in the Cornea. Biomolecules 2019, 9, 785.

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